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hereditary spastic paraplegia 35 - Clinical Profile, Genes & Research | Kisho | Kisho

Features include very common findings: Lower limb spasticity, Overactive reflexes (hyperreflexia), Babinski sign, and Difficulty walking (gait disturbance) and others; and common findings: Dysmetria, Dystonia, Shrinkage of the cerebellum (cerebellar atrophy), and Thin corpus callosum and others. 47 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	18	Dystonia, Seizure, Ataxia
Muscles	9	Shrinkage of the cerebellum (cerebellar atrophy), Atrophy/Degeneration affecting the brainstem, Damage to the optic nerve (optic atrophy)
Eyes	4	Strabismus, Nystagmus, Damage to the optic nerve (optic atrophy)
Arms and legs	4	Lower limb spasticity, Foot dorsiflexor weakness, Lower limb hypertonia
Kidneys and urinary system	2	Urinary incontinence, Urinary urgency
Bones and joints	1	Excessive outward curvature of the upper spine (kyphosis)

GeneReviews

Clinical Guidance

Fatty acid hydroxylase-associated neurodegeneration (FAHN) is characterized early in the disease course by central nervous system involvement including corticospinal tract involvement (spasticity), mixed movement disorder (ataxia/dystonia), eye findings (optic atrophy, oculomotor abnormalities), and later in the disease course by progressive intellectual impairment and seizures. FAHN is a subtype of neurodegeneration with brain iron accumulation (NBIA) but is also included under the classifications of leukodystrophies and hereditary spastic paraplegias.

Source: GeneReviews — "Fatty Acid Hydroxylase-Associated Neurodegeneration"

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

Fatty acid hydroxylase-associated neurodegeneration (FAHN) should be considered in individuals with the following clinical findings, neuroimaging findings, and family history .

Clinical findings

Source: GeneReviews — "Fatty Acid Hydroxylase-Associated Neurodegeneration"

GeneReviews

Differential Diagnosis

Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a neurodegenerative disorder that shows clinical overlap with other early-onset neurodegenerative disorders. Disorders that may exhibit clinical and neuroimaging features similar to those seen in FAHN are summarized in . Table 2. Disorders to Consider in the Differential Diagnosis of FAHN

Phenotype	DiffDx Disorder	Gene(s)	MOI	Additional Clinical MRI Features of DiffDx Disorder
C19orf12	AR	Cognitive decline; Progressive spasticity dystonia; Optic atrophy	Hyperintense streaking of medial medullary lamina often observed on T2-weighted MRI; Parkinsonism developing in later disease PKAN	—
PANK2	AR	Progressive dystonia dysarthria

Genetic testing for FA2H is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for hereditary spastic paraplegia 35 has been reported in the published literature.

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for hereditary spastic paraplegia 35. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with fatty acid hydroxylase-associated neurodegeneration (FAHN), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Fatty Acid Hydroxylase-Associated Neurodegeneration (FAHN)

System/Concern	Evaluation	Comment
Eyes	Ophthalmologic eval	To incl visual acuity exam for optic atrophy or eye movement abnormalities
Feeding	Multidisciplinary team eval	Attn to nutritional status feeding
Musculoskeletal	PT OT	Mobility self-help skills
Neurologic	Neurologic eval	For dystonia, ataxia, spasticity; incl EEG if question of seizures. Miscellaneous/
Other	Developmental assessment	To incl motor, general cognitive, vocational skills Speech language pathologist

Source: GeneReviews — "Fatty Acid Hydroxylase-Associated Neurodegeneration"

GeneReviews

Therapies Under Investigation

Iron chelation. Interest in iron chelation has reemerged as trials using deferiprone have been published in other disorders of brain iron accumulation, including Friedreich ataxia and superficial siderosis . Deferiprone can cross the blood-brain barrier and remove intracellular iron. A multicenter, placebo controlled, double-blind trial comparing the efficacy and safety of 18 months of treatment with deferiprone versus placebo in patients with PKAN was completed in January of 2017 (see Clinical Trials). Data are currently being analyzed. Results, when published, may be generalizable to other NBIA disorders. However, long-term clinical trials of deferiprone in specific forms of NBIA will be necessary to further assess safety and efficacy. Search ClinicalTrials.

Source: GeneReviews — "Fatty Acid Hydroxylase-Associated Neurodegeneration"

Clinical Trials

View trials for hereditary spastic paraplegia 35

Explore Trials

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for hereditary spastic paraplegia 35.

14 publications have been identified in PubMed for hereditary spastic paraplegia 35. Research spans Case Report / Case Series (29%), Review / Meta-Analysis (21%), and Epidemiology / Natural History (21%).

Research Type	Count	% of Total
Patient case studies	4	29%
Research summaries	3	21%
Disease patterns and progression	3	21%
Testing and diagnosis research	2	14%
Clinical study results	1	7%
Laboratory research	1	7%

Recent Publications

Erhardt C (2026). [PMID: 41774218](https://pubmed.ncbi.nlm.nih.gov/41774218/). *Metab Brain Dis*. [Clinical Trial Publication]
Sobanska A (2026). [PMID: 41507865](https://pubmed.ncbi.nlm.nih.gov/41507865/). *BMC Neurol*. [Epidemiology / Natural History]
Lin PY (2026). [PMID: 40518753](https://pubmed.ncbi.nlm.nih.gov/40518753/). *Acta Neurol Taiwan*. [Epidemiology / Natural History]
Roy S (2026). [PMID: 41006743](https://pubmed.ncbi.nlm.nih.gov/41006743/). *Acta Neurol Belg*. [Case Report / Case Series]
Holla VV (2026). [PMID: 41798181](https://pubmed.ncbi.nlm.nih.gov/41798181/). *Tremor Other Hyperkinet Mov (N Y)*. [Review / Meta-Analysis]
Salari M (2025). [PMID: 40041249](https://pubmed.ncbi.nlm.nih.gov/40041249/). *Neurol Genet*. [Review / Meta-Analysis]
Yigit ZM (2025). [PMID: 40782215](https://pubmed.ncbi.nlm.nih.gov/40782215/). *Neurogenetics*. [Case Report / Case Series]
de Vries BS (2025). [PMID: 40388677](https://pubmed.ncbi.nlm.nih.gov/40388677/). *Neurology*. [Diagnostic / Biomarker]
Lan SC (2025). [PMID: 40397273](https://pubmed.ncbi.nlm.nih.gov/40397273/). *Mol Biol Rep*. [Case Report / Case Series]
Rudenskaya GE (2025). [PMID: 40457680](https://pubmed.ncbi.nlm.nih.gov/40457680/). *Zh Nevrol Psikhiatr Im S S Korsakova*. [Review / Meta-Analysis]

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hereditary spastic paraplegia 35

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

hereditary spastic paraplegia 35

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team